To investigate, based on a putative abnormal neural processing of disgusting signals in Prader Willi syndrome (PWS) patients, the brain response to visual representations of disgusting food in PWS using functional MRI (fMRI). Twenty-one genetically-confirmed PWS patients, 30 age- and sex-matched and 28 BMI-matched control subjects viewed a movie depicting disgusting food-related scenes interspersed with scenes of appetizing food while fMRI was acquired. Brain activation maps were compared between groups and correlated with disgust and hunger ratings. At the cortical level, the response to disgusting food representations in PWS patients was qualitatively similar to that of control subjects, albeit less extensive, and engaged brain regions typically related to visually-evoked disgust, such as the anterior insula/frontal operculum, the lateral frontal cortex and visual areas. By contrast, activation was almost absent in limbic structures directly concerned with the regulation of instinctive behavior robustly activated in control subjects, such as the hypothalamus, amygdala/hippocampus and periaqueductal gray. Our study provides novel insights into the neural substrates of appetite control in a genetically-mediated cause of obesity. The presence of significant cortical changes further indicates that PWS patients consciously process disgusting stimuli, but the virtual absence of response in deep, limbic structures suggests that disgusting signals do not adequately reach the primary brain system for the appetite control.

We compared body composition, biochemical parameters, motor function, and brain neural activation in 27 adults with Prader–Willi syndrome and growth-hormone deficiency versus age-and sex-matched controls and baseline versus posttreatment values of these parameters after one year of recombinant human growth hormone (rhGH) treatment. To study body composition, we analyzed percentage of fat mass, percentage of lean mass, and muscle-mass surrogate variables from dual X-ray absorptiometry. Biochemical parameters analyzed included IGF-I, glucose metabolism, and myokines (myostatin, irisin, and IL6). To explore muscle function, we used dynamometer-measured handgrip strength, the Timed Up and Go (TUG) test, and the Berg Balance Scale (BBS). To study brain activation, we acquired functional magnetic resonance images during three motor tasks of varying complexity. After one year of treatment, we observed an increase in lean mass and its surrogates, a decrease in fat mass, improvements in TUG test and BBS scores, and increased neural activation in certain cerebellar areas. The treatment did not significantly worsen glucose metabolism, and no side-effects were reported. Our findings support the benefits of rhGH treatment in adults with Prader–Willi syndrome and growth-hormone deficiency on body composition and suggest that it may also improve balance and brain neural activation.

Severe hypotonia during infancy is a hallmark feature of Prader Willi syndrome (PWS). Despite its transient expression, moto development is delayed and deficiencies in motor coordination are present at older ages, with no clear pathophysiological mechanism yet identified. The diverse motor coordination symptoms present in adult PWS patients could be, in part, the result of a common alteration(s) in basic motor control systems. We aimed to examine the motor system in PWS using functional MRI (fMRI) during motor challenge. Twenty-three adults with PWS and 22 matched healthy subjects participated in the study. fMRI testing involved three hand motor tasks of different complexity. Additional behavioral measurements of motor function were obtained by evaluating hand grip strength, functional mobility, and balance. Whole brain activation maps were compared between groups and correlated with behavioral measurements. Performance of the motor tasks in PWS engaged the neural elements typically involved in motor processing. While our data showed no group differences in the simplest task, increasing task demands evoked significantly weaker activation in patients in the cerebellum. Significant interaction between group and correlation pattern with measures of motor function were also observed. Our study provides novel insights into the neural substrates of motor control in PWS by demonstrating reduced cerebellar activation during movement coordination.

Obesity and growth hormone (GH)-deficiency are consistent features of Prader–Willi syndrome (PWS). Centrally, kisspeptin is involved in regulating reproductive function and can stimulate hypothalamic hormones such as GH. Peripherally, kisspeptin signaling influences energy and metabolic status. We evaluated the effect of 12-month GH treatment on plasma kisspeptin levels in 27 GH-deficient adult PWS patients and analyzed its relationship with metabolic and anthropometric changes. Twenty-seven matched obese subjects and 22 healthy subjects were also studied. Before treatment, plasma kisspeptin concentrations in PWS and obese subjects were similar (140.20 (23.5–156.8) pg/mL vs. 141.96 (113.9–165.6) pg/mL, respectively, p = 0.979)) and higher (p = 0.019) than in healthy subjects (124.58 (107.3–139.0) pg/mL); plasma leptin concentrations were similar in PWS and obese subjects (48.15 (28.80–67.10) ng/mL vs. 33.10 (20.50–67.30) ng/mL, respectively, p = 0.152) and higher (p < 0.001) than in healthy subjects (14.80 (11.37–67.30) ng/mL). After GH therapy, lean body mass increased 2.1% (p = 0.03), total fat mass decreased 1.6% (p = 0.005), and plasma kisspeptin decreased to levels observed in normal-weight subjects (125.1(106.2–153.4) pg/mL, p = 0.027). BMI and leptin levels remained unchanged. In conclusion, 12-month GH therapy improved body composition and decreased plasma kisspeptin in GH deficient adults with PWS. All data are expressed in median (interquartile range).

Introduction: Prader Willi syndrome (PWS) is the most common syndromic form of obesity, caused by the absence of expression of the paternally active gens on the long arm of chromosome 15.The 16p11.2 microdeletion has recently been recognized as a syndromic condition appearing to be a predisposing factor for overweight, being the second most common genetic cause of obesity. One possible causative gen- SH2B1- involving leptin and insulin signaling, has been identified, although other genes may play a role. Case report: We describe a case series of seven patients diagnosed with 16p11.2 deletion in our hospital between 2013–2015 and compare their main features with PWS. Four of them were men with an average age at diagnosis of 9.9±6.1 years. Two of them were referred to our clinical genetics department with a suspected diagnosis of PWS. Five of them had a sex-specific BMI for age over 95th percent. The mean length of deletion was 530.7Kb [448–598].Two of them suffered seizures and one patient had sleep apnoea.In the same way as PWS individuals, patients with 16p11.2 deletion present with hypotonia at birth. They may exhibit developmental delay, intellectual disability, and/or autism spectrum disorder. Weight is variable in childhood, but hyperphagia and obesity usually starts from one year on in PWS and later in 16p11.2 deletion. On the other hand, individuals with 16p11.2 syndrome don’t have short stature nor other hormonal deficiencies as PWS individuals do (thyroid or reproductive axis). They can suffer from minor cardiac malformations but not from scoliosis. Conclusions: Since the implementation of array analysis, numerous microdeletion syndromes as 16p11.2 have been described. Further research is needed for a comprehensive characterization of a genotype-phenotype correlation. It should be considered as one of the genetic causes of obesity following PWS. It’s important to identify clinical characteristics, leading to perform genetic testing and counseling.

Introduction: Most serum cortisol (SeC) is linked to cortisol binding globulin and albumin. When the synthesis of proteins is reduced or increased, SeC does not reflect the actual free cortisol (FC) (active fraction). Methods for FC analysis are very laborious and expensive, which makes difficult to use them as a routine laboratory tests. Salivary cortisol (SaC) mirrors the FC in serum, being its measurement easier and cheaper. The determination of SaC, instead of total cortisol after stimulation with ACTH, has been proposed as an alternative for adrenal insufficiency diagnosis, but this test has not been standardized yet. The goal of this study is to determinate the reference values for SaC after stimulation with 250 μg of ACTH i.v. and their correlation with those for SeC. Methods and design: Forty-five healthy volunteers and 39 patients with known adrenal insufficiency (primary or secondary) were included. After at least 8 h fast, serum and saliva samples were collected before and after the administration of 250 μg of ACTH i.v. for the determination of cortisol in times: 0′, 30′, 60′ and 90′. Patients received their last dosage of hidrocortisone at 0900 h the day before. Results: All healthy volunteers had a SeC peak at 30 min ≥18 μg/dl. Healthy volunteers SaC [mean±SD (range), μg/dl] was: 0′:0.56±0.31(0.08–1.37); 30′;1.58±0.45(0.83–2.72); 60′:2.35±0.63(1.43–4.24); 90′:2.91±0.82(1.63–5.42). Patients SaC [mean±SD (range), μg/dl] was: 0′:0.33±0.30(0.05–1.53); 30′:0.32±0.24(0.05–1.17) 60′:0.32±0.24(0.05–0.90); 90′:0.37±0.50(0.05–3.13). The SaC correlated with SeC at all times, except in time 0′ for the group of patients. Healthy volunteers lower limit value SaC at 60′ was 1.43 μg/dl. This cut-off classified all patients correctly. Conclusion: Measurement of SaC offers an alternative to SeC ACTH stimulation test (250 μg). We suggest that adrenal insufficiency can be excluded when SaC at 60′ is ≥1.43 μg/dl.